1. Field of the Invention
The present invention relates to S-sulfonated calcitonin derivatives, a process for a production thereof, and the use thereof. The present S-sulfonated calcitonin derivatives are promising for use in the drug therapy of osteoprosis, hypercalcemia, and Paget's disease and the like, as well as for a stimulation of osteogenesis.
2. Description of Related Art
Calcitonins are well known as polypeptides exhibiting an activity of lowering a serum calcium level. Calcitonins are secreted from a thyroid gland of mammals such as humans, porcines, bovines, sheep and the like, as well as an ultimobranchial body of, for example, fowls and fishes such as salmon and eel and the like, amphibia, and reptiles and the like. These calcitonins have been isolated and purified, and their amino acid sequences determined.
Recently, various kinds of calcitonins and calcitonin-like substances prepared by chemical synthesis or gene recombination techniques have been reported, and among them, salmon calcitonins, eel calcitonin, porcine calcitonin, human calcitonin and the like have been clinically used.
All of these various kinds of calcitonins have a common structure in that they consist of 32 amino acid residues wherein the first amino acid and the seventh amino acid are L-cysteine, and mercapto radicals of the L-cysteine residues together form a disulfide bridge. It is believed that this disulfide bridge between the first amino acid and the seventh amino acid, or an ethylene linkage between these amino acids, is an essential structure for the exhibition of the biological activities of calcitonins.
Unfortunately, the presence of the disulfide bridge in question in calcitonins makes them physiochemically unstable, resulting in a degradation thereof during their purification processes and storage, as well as difficulties in their formulation. Moreover, it is believed that a short in vivo half-life of calcitonin partly results from the disruption of the disulfide bridge in question by endogeneous enzymes.